Abstract

Takeda Vaccines Inc., is developing a live attenuated tetravalent Dengue vaccine candidate (TDV) that consists of an attenuated DENV-2 strain (TDV-2) and three chimeric viruses containing the prM and E protein genes of DENV-1, -3 and -4 expressed in the context of the attenuated TDV-2 genome backbone (TDV-1, TDV-3, and TDV-4, respectively). A better understanding on how innate immune responses to recipients of TDV vaccine shape adaptive immunity is essential for the development of a safe and effective vaccine. In project 2 of the Dengue Human Immunology Project Consortium (DHIPC) we apply a systems biology approach to dissect the qualitative and quantitative features of the innate and adaptive immune responses generated by TDV. The overall goal of Project 2 is to identify gene expression signatures following TDV vaccination that will be correlated to measurements of tetravalent neutralizing antibody titers and/or the magnitude and multifunctionality of T cell responses. This should enable identifying markers predictive of vaccine immunogenicity and efficacy. The innate immune signatures acquired in Project 2 will be compared to those obtained in parallel investigations of samples from natural human DENV infections (Project 1) and ex vivo infection of relevant primary immune cells with the same viruses to gain mechanistic insight (Project 3).

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19AI118610-01
Application #
8929554
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2015-07-01
Budget End
2016-06-30
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost

  Institution

Name
Icahn School of Medicine at Mount Sinai
Department
Type
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029

  Publications

Amir, El-Ad David; Guo, Xinzheng V; Mayovska, Oksana et al. (2018) Average Overlap Frequency: A simple metric to evaluate staining quality and community identification in high dimensional mass cytometry experiments. J Immunol Methods 453:20-29
Premkumar, Lakshmanane; Collins, Matthew; Graham, Stephen et al. (2018) Development of Envelope Protein Antigens To Serologically Differentiate Zika Virus Infection from Dengue Virus Infection. J Clin Microbiol 56:
Balmaseda, Angel; Zambrana, José Victor; Collado, Damaris et al. (2018) Comparison of Four Serological Methods and Two Reverse Transcription-PCR Assays for Diagnosis and Surveillance of Zika Virus Infection. J Clin Microbiol 56:
Kalayci, Selim; Gümü?, Zeynep H (2018) Exploring Biological Networks in 3D, Stereoscopic 3D, and Immersive 3D with iCAVE. Curr Protoc Bioinformatics 61:8.27.1-8.27.26
Katzelnick, Leah C; Ben-Shachar, Rotem; Mercado, Juan Carlos et al. (2018) Dynamics and determinants of the force of infection of dengue virus from 1994 to 2015 in Managua, Nicaragua. Proc Natl Acad Sci U S A 115:10762-10767
Mishra, Nischay; Caciula, Adrian; Price, Adam et al. (2018) Diagnosis of Zika Virus Infection by Peptide Array and Enzyme-Linked Immunosorbent Assay. MBio 9:
Janssens, Sylvie; Schotsaert, Michael; Manganaro, Lara et al. (2018) FACS-Mediated Isolation of Neuronal Cell Populations From Virus-Infected Human Embryonic Stem Cell-Derived Cerebral Organoid Cultures. Curr Protoc Stem Cell Biol :e65
Thézé, Julien; Li, Tony; du Plessis, Louis et al. (2018) Genomic Epidemiology Reconstructs the Introduction and Spread of Zika Virus in Central America and Mexico. Cell Host Microbe 23:855-864.e7
Patil, Veena S; Madrigal, Ariel; Schmiedel, Benjamin J et al. (2018) Precursors of human CD4+ cytotoxic T lymphocytes identified by single-cell transcriptome analysis. Sci Immunol 3:
Manganaro, Lara; Hong, Patrick; Hernandez, Matthew M et al. (2018) IL-15 regulates susceptibility of CD4+ T cells to HIV infection. Proc Natl Acad Sci U S A 115:E9659-E9667

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